Exomic and transcriptomic alterations of hereditary gingival fibromatosis.

OBJECTIVE: Hereditary gingival fibromatosis (HGF) is a rare oral disease characterized by either localized or generalized gradual, benign, non-hemorrhagic enlargement of gingivae. Although several genetic causes of HGF are known, the genetic etiology of HGF as a non-syndromic and idiopathic entity remains uncertain. SUBJECTS AND METHODS: We performed exome and RNA-seq of idiopathic HGF patients and controls, and then devised a computational framework that specifies exomic/transcriptomic alterations interconnected by a regulatory network to unravel genetic etiology of HGF. Moreover, given the lack of animal model or large-scale cohort data of HGF, we developed a strategy to cross-check their clinical relevance through in silico gene-phenotype mapping with biomedical literature mining and semantic analysis of disease phenotype similarities. RESULTS: Exomic variants and differentially expressed genes of HGF were connected by members of TGF-ß/SMAD signaling pathway and craniofacial development processes, accounting for the molecular mechanism of fibroblast overgrowth mimicking HGF. Our cross-check supports that genes derived from the regulatory network analysis have pathogenic roles in fibromatosis-related diseases. CONCLUSIONS: The computational approach of connecting exomic and transcriptomic alterations through regulatory networks is applicable in the clinical interpretation of genetic variants in HGF patients.

Alveolar regions of the mandible for the installation of immediate-implant fixtures and bone screws of alveolar distractors.

The purposes of this study were to elucidate the anatomic relationship between the dental roots and surrounding tissues and to identify the optimal sites at which to install dental surgical devices including immediate-implant fixtures and alveolar distractors. We made 5 types of measurements on horizontal cross sections obtained at 1-mm intervals from 20 Korean mandibles. The following results were obtained: (1) the mandibular facial plate was thinnest at the canine (0.5-0.7 mm) and became thicker toward the molar region; (2) the thicknesses of the facial and lingual cortical bone in the interdental region increased from anterior to posterior and from coronal to apical aspects; (3) in each section, the buccolingual root was narrower than 4 mm at depths greater than 8 and 9 mm in the central and lateral incisors, respectively, and the maximum mesiodistal root widths were 3.0 and 3.3 mm; (4) the interroot distance increased from anterior to posterior and from coronal to apical aspects; and (5) on the sections of the first and second molars, the diameter of the septal bone ranged from 4.2 to 7.9 mm buccolingually and from 1.3 to 3.3 mm mesiodistally. Achieving successful placements of implant fixtures and bone screws requires an accurate understanding of the anatomic structure at the installation site. The reported anatomic data might facilitate successful treatments and provide crucial information for use when planning and performing placements of dental surgical devices.

Morphometric analysis of the anterior region of the maxillary bone for immediate implant placement using micro-CT.

The purpose of this study was to elucidate the relationship between the maxillary incisor roots and surrounding alveolar structures using microscopic computerized tomography (micro-CT) for the immediate implant placement. Nineteen maxillae from 14 Korean cadavers were used in this study. All specimens were scanned and reconstructed into a three-dimensional (3D) structure using a micro-CT system. The roots of the maxillary central and lateral incisors became dramatically narrower from 6 mm above the cementoenamel junctions to the apex. The roots of the maxillary incisors and canine were located at the labial one fifths region of the alveolar bone. The angle formed by the longitudinal root axis and the alveolar bone was greatest at the maxillary canine. On the basis of the results of this study, guidelines for immediate implant placement can be suggested on the implant diameter and drilling angle to minimize damage of the alveolar plate.

Influence of a microgrooved collar design on soft and hard tissue healing of immediate implantation in fresh extraction sites in dogs.

OBJECTIVE: This study compared the alveolar bone reduction after immediate implantation using microgrooved and smooth collar implants in fresh extracted sockets. MATERIAL AND METHODS: Four mongrel dogs were used in this study. The full buccal and lingual mucoperiosteal flaps were elevated and the third and fourth premolars of the mandible were removed. The implants were installed in the fresh extracted sockets. The animals were sacrificed after a 3-month healing period. The mandibles were dissected and each implant site was removed and processed for a histological examination. RESULTS: During healing, the marginal gaps in both groups, which were present between the implant and the socket walls at implantation, disappeared as a result of bone filling and resorption of the bone crest. The buccal bone crests were located apical of its lingual counterparts. At the 12-week interval, the mean bone-implant contact in the microgrooved group was significantly higher than that of the turned surface group. From the observations in some of the microgrooved groups, we have found bone attachment to the 12 mum microgrooved surface and collagen fibers perpendicular to the long axis of the implants over the 8 mum microgrooved surface. CONCLUSION: Within the limitations of this study, microgrooved implants may provide more favorable conditions for the attachment of hard and soft tissues and reduce the level of marginal bone resorption and soft tissue recession.

Influence of transmucosal designs of three one-piece implant systems on early tissue responses: a histometric study in beagle dogs.

PURPOSE: The purpose of this study was to investigate the early tissue response around three one-piece implant systems with different transmucosal designs. MATERIALS AND METHODS: Three one-piece dental implant systems with different profiles and surface roughnesses on the transmucosal portion were examined in the current study. The transmucosal portions were flared and machined (FM), concave and machined with microgrooves (CMG), or straight and anodic oxidized (SA). A total of 30 implants (10 of each type) were placed in computer-generated randomized order in the mandibular residual ridges of five beagle dogs. Six months later, all animals were sacrificed and histologic sections were prepared to measure epithelial tissue height, connective tissue contact, and the amount of bone resorption. One-way analysis of variance and the Bonferroni post hoc test were used for statistical evaluation (alpha = 95%). RESULTS: After a 6-month nonfunctional loading period, all 30 implants were clinically immobile. Slight swelling and redness of the peri-implant soft tissue were noticed around most of the implant abutments. Histometric analysis showed that the FM implants had a longer epithelial tissue height than the CMG implants. The CMG implants showed the greatest amount of connective tissue attachment among the three groups and the least amount of marginal bone resorption. The CMG and SA implants showed bone growth above the initial reference point at 10 and 7 measurement sites, respectively, whereas no bone overgrowth was noted around the FM implants. CONCLUSION: Based on this study conducted in five beagle dogs, a concave transmucosal profile with a microgrooved surface was associated with longer connective tissue attachments and less bone resorption versus implants that were flared with a machined surface or straight with an anodic oxidized surface in the early healing phase. Int J Oral Maxillofac Implants 2010;25:309-314.

Genetic investigation of bisphosphonate-related osteonecrosis of jaw (BRONJ) via whole exome sequencing and bioinformatics.

Complications associated with the use of bisphosphonate (BP) have risen over the years due to an increase in the prescription of BP. BP-related osteonecrosis of jaw (BRONJ), one of the complications linked to the consumption of BP, greatly affects patients with minor dental trauma, incurring a long healing period. While BRONJ afflicts only a minority of patients prescribed with BP, BRONJ is a multigenic disease affected both by environmental and genetic factors having a distinctive phenotype. This study aims to discover genetic biomarkers associated with BRONJ via whole exome sequencing (WES) followed by statistical analysis. Sixteen individuals who had been prescribed with bisphosphonate medication and diagnosed as BRONJ were chosen and each individual's saliva sample was collected for WES. 126 randomized subsamples from the GSK project representing 109 male and 17 female Koreans were used as a control data set. Fisher's exact test was carried out to assess the significance of genetic variants in BRONJ patients. Gene set enrichment analysis (GSEA) (DAVID Bioinformatics Resource 6.7) was used to perform a cluster analysis of variants found from Fisher's exact test. The results from this study suggest that BRONJ-inducing factors are genetically associated and BRONJ occurs due to the malfunctioning of post-translational modification in osteoclast leading to the impairment of cell morphology and adhesion.

Multifactorial evaluation of implant failure: a 19-year retrospective study.

PURPOSE: Dental implants generally provide good results as replacements for missing teeth, but a few patients experience implant failure. The aim of this retrospective study was to analyze the characteristics and causes of implant failures in hopes of reducing future failures. MATERIALS AND METHODS: Patients who received one or more implants at the Dental Hospital of Yonsei University College of Dentistry between February 1991 and May 2009 were included in this study. Data including age, sex, medical history, habits (eg, smoking and drinking), bone quality, primary stability, implant size, implant surface, additional surgical procedures, prosthetic type, clinical symptoms, implant failure date, and causes of implant failure were obtained through a chart review. Follow-up radiographs were compared to those obtained at baseline. The Pearson chi-square test and Fisher exact test were used to evaluate the correlations between risk factors and implant failure. RESULTS: In total, 879 patients received 2,796 implants; 150 implants in 91 patients had failed. Early and late implant failures occurred with 86 (57.3%) and 64 (42.7%) implants, respectively. The main causes of early and late implant failures were inflammation (47%) and overloading (53%), respectively. When the cause of early implant failure was inflammation, the failure rate was significantly higher for implants in the anterior maxilla; implants with poor primary stability, a machined surface, or a length exceeding 15 mm; and implants placed with a reconstructive procedure and two-stage surgery. When late implant failure was caused by overloading, the failure rate was significantly higher for implants with a machined surface, placed with a reconstructive procedure and/or two-stage surgery, and supporting telescopic dentures. CONCLUSION: Within the limitations of this study, the major causes of implant failure are inflammation and overloading, and they differ between early and late implant failures.

Investigation of pathogenic genes in peri-implantitis from implant clustering failure patients: a whole-exome sequencing pilot study.

Peri-implantitis is a frequently occurring gum disease linked to multi-factorial traits with various environmental and genetic causalities and no known concrete pathogenesis. The varying severity of peri-implantitis among patients with relatively similar environments suggests a genetic aspect which needs to be investigated to understand and regulate the pathogenesis of the disease. Six unrelated individuals with multiple clusterization implant failure due to severe peri-implantitis were chosen for this study. These six individuals had relatively healthy lifestyles, with minimal environmental causalities affecting peri-implantitis. Research was undertaken to investigate pathogenic genes in peri-implantitis albeit with a small number of subjects and incomplete elimination of environmental causalities. Whole-exome sequencing was performed on collected saliva samples via self DNA collection kit. Common variants with minor allele frequencies (MAF) > = 0.05 from all control datasets were eliminated and variants having high and moderate impact and loss of function were used for comparison. Gene set enrichment analysis was performed to reveal functional groups associated with the genetic variants. 2,022 genes were left after filtering against dbSNP, the 1000 Genomes East Asian population, and healthy Korean randomized subsample data (GSK project). 175 (p-value <0.05) out of 927 gene sets were obtained via GSEA (DAVID). The top 10 was chosen (p-value <0.05) from cluster enrichment showing significance of cytoskeleton, cell adhesion, and metal ion binding. Network analysis was applied to find relationships between functional clusters. Among the functional groups, ion metal binding was located in the center of all clusters, indicating dysfunction of regulation in metal ion concentration might affect cell morphology or cell adhesion, resulting in implant failure. This result may demonstrate the feasibility of and provide pilot data for a larger research project aimed at discovering biomarkers for early diagnosis of peri-implantitis.

Morphometric analysis of maxillary alveolar regions for immediate implantation.

PURPOSE: The purpose of this study was to provide an actual guideline in determining the shape, diameter, and position of the implant in immediate implantation by the measurement of the thickness of facial and palatal plate, the thickness of cortical bone on the facial and palatal plate, the diameter of the root, and the distance between the roots in the cadavers. MATERIALS AND METHODS: The horizontal sections of 20 maxillae were measured and analyzed to obtain the average values. Resin blocks were produced and cut serially at 1 mm intervals from the cervical line to the root apex. Images of each section were obtained and the following measurements were performed: The thickness of the facial and palatal residual bone at each root surface, the thickness of the facial and palatal cortical bone at the interdental region, the diameter of all roots of each section on the faciopalatal and mesiodistal diameter, and the interroot distance. Three specimens with measurements close to the average values were chosen and 3-dimensional images were reconstructed. RESULTS: The thickness of the facial and palatal cortical bone at the interdental region in the maxilla, the buccal cortical bone was thicker in the posterior region compared to the anterior region. The interroot distance of the alveolar bone thickness between the roots increased from anterior to posterior region and from coronal to apical in the maxilla. CONCLUSION: In this study, the limited results of the morphometric analysis of the alveolar ridge using the sections of maxilla in the cadavers may offer the useful information when planning and selecting optimal implant for immediate implantation in the maxilla.